在很长一段时期内，疟原虫与人类免疫系统的游击战都取得了胜利，在本周的《生物化学杂志》（JBC）上有一篇研究报道，揭露了疟原虫躲避免疫蛋白的一种诡计，有可能成为未来药物开发的标靶。
疟疾寄生虫（疟原虫）是通过蚊子感染人的。一旦进入人类宿主后，这种寄生虫就会在肝脏细胞安营扎寨，然后进入血红细胞（RBCs）进行复制，等待下一只蚊子来继续这个过程。
疟原虫感染血细胞后，它们会向细胞表面释放出一系列粘性蛋白质，使其能够附着在血管上，以便逃避它们复制时宿主脾脏对它们的破坏。这一过程尤其会给怀孕期妇女带来严重问题，感染疟疾的RBCs会聚集在血管丰富的胎盘（它是胎儿生长时食物和氧气的来源），并造成许多健康问题，如贫血、低出生体重、发烧等等。
但是，以这些粘性蛋白质作为药物靶标非常困难，这是由于疟原虫用于侵入人类免疫系统的蛋白质种类很多。然而，这种蛋白质的某些部位仍旧会保持特定功能，在这篇研究报道中，Matthew Higgins绘制了一个高分辨率三维结构，它是疟原虫与胎盘结合的粘性蛋白质——PfEMP1，用以研究疟原虫如何保护这些保守区域。
Higgins发现，PfEMP1的一个可变区遮盖着另一个区域，被遮盖的这个区域对蛋白质锚定到胎盘壁上具有重要作用。当被感染的RBCs接近硫酸软骨素时——一种血管壁上的结构分子，这个可变区就会转到另一侧，暂时性的把结合域暴露出来，使其能够在适当位置锚定。
Higgins认为，在疟疾高发地区的妇女会在多次怀孕并引起RBCs在胎盘聚集之后，通过对PfEMP1的免疫应答反应而获得一部份免疫性。针对这种蛋白质的保守结合域，用硫酸软骨素的结构类似药物刺激使其暴露在外，是一种加强产生免疫力的方法。
原始出处：
JBC，Vol. 283, Issue 32, 21842-21846，Matthew K. Higgins
From the Department of Biochemistry, University of Cambridge, 80, Tennis Court Road, Cambridge CB2 1GA, United Kingdom
Received for publication, April 24, 2008 , and in revised form, June 3, 2008.
Adhesive PfEMP1 proteins are displayed on the surface of malaria-infected red blood cells. They play a critical role in the disease, tethering infected cells away from destruction by the spleen and causing many severe symptoms. A molecular understanding of how these domains maintain their binding properties while evading immune detection will be important in developing therapeutics. In malaria of pregnancy, domains from the var2csa-encoded PfEMP1 protein interact with chondroitin sulfate on the placenta surface. This causes accumulation of infected red blood cells, leading to placental inflammation and block of blood flow to the developing fetus. This is associated with maternal anemia, low birth weight, and premature delivery and can lead to the death of mother and child. Here I present the structure of the chondroitin sulfate-binding DBL3X domain from a var2csa-encoded PfEMP1 protein. The domain adopts a fold similar to malarial invasion proteins, with extensive loop insertions. One loop is flexible in the unliganded structure but observed in the presence of sulfate or disaccharide, where it completes a sulfate-binding site. This loop, and others surrounding this putative carbohydrate-binding site, are flexible and polymorphic, perhaps protecting the binding site from immune detection. This suggests a model for how the domain maintains ligand binding while evading the immune response and will guide future drug and vaccine development.
